Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia

NCT01020539 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: AAAA6378CHNY-504
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic stem cell transplantation (AlloSCT) followed by targeted immune therapy Gemtuzumab Ozogamicin patients with acute myeloid leukemia (AML)/juvenile myelomonocytic leukemia (JMML)/myelodysplastic syndromes (MDS) will be safe and well tolerated.

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Juvenile Myelomonocytic Leukemia

Keywords

Allogeneic Stem Cell Transplantation; Targeted Immune Therapy; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Juvenile Myelomonocytic Leukemia; AML; MDS; JMML

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO)

  To determine the maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (anti CD33 immunotoxin) therapy following reduced intensity (RI) allogeneic stem cell transplantation (alloSCT) in patients with average risk AML/JMML/MDS.

  Up to 2 years

Secondary Outcomes (5)

• Change of minimal residual disease

  Day 60, Day 100, Day 180, 1 year, 2 years

• Incidence of minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue

  Up to 2 years

• Degree of mixed/complete donor chimerism

  Up to 2 years

• Event free survival (EFS) rate

  Up to 2 years

• Overall survival (OS) rate

  Up to 2 years

Study Arms (2)

Matched Family Donor

EXPERIMENTAL

Patients will receive a reduced intensity fludarabine (6 days)/busulfan (2 days) conditioning regimen followed by a stem cell transplant from a related family donor using bone marrow or cord blood stem cells. Then followed by Gemtuzumab Ozogamicin, once at about 2-6 months post alloSCT and once at least 2 months after the first dose. Patients with JMML will also receive cis-retinoic acid (Isotretinoin). During and following transplantation patients will receive methylprednisolone for immune suppression. Graft-versus-host-disease (GVHD) prophylaxis will consist of tacrolimus, mycophenolate mofetil and additionally methotrexate in recipients of unrelated adult transplants.

Drug: Fludarabine; Drug: Busulfan; Drug: GVHD Prophylaxis; Drug: Gemtuzumab Ozogamicin

Unrelated Donor

EXPERIMENTAL

Patients will receive a reduced intensity fludarabine (6 days)/busulfan (2 days) conditioning regimen followed by a stem cell transplant from an unrelated donor using matched bone marrow or cord blood stem cells.Then followed by Gemtuzumab Ozogamicin, once at about 2-6 months post alloSCT and once at least 2 months after the first dose. Patients with JMML will also receive cis-retinoic acid (Isotretinoin). During and following transplantation patients will receive methylprednisolone for immune suppression and unrelated donor transplant recipients will additionally receive Anti-Thymocyte Globulin. GVHD prophylaxis will consist of tacrolimus, mycophenolate mofetil and additionally methotrexate in recipients of unrelated adult transplants.

Drug: Anti-Thymocyte Globulin; Drug: Isotretinoin

Interventions

Fludarabine DRUG

Conditioning Regimen

Also known as: Fludara®

Matched Family Donor

Busulfan DRUG

Conditioning Regimen

Also known as: Busulfex®

Matched Family Donor

GVHD Prophylaxis DRUG

Can be FK506 (Tacrolimus/Prograf®), mycophenolate mofetil ((MMF)/Cellcept®), or methotrexate (MTX, amethopterin)

Matched Family Donor

Gemtuzumab Ozogamicin DRUG

Dose Escalation

Also known as: Mylotarg®

Matched Family Donor

Anti-Thymocyte Globulin DRUG

Unrelated Donors only

Also known as: Thymoglobulin®

Unrelated Donor

Isotretinoin DRUG

JMML patients only

Also known as: Accutane®, 13-cis-Retinoic Acid (cis-RA)

Unrelated Donor

Eligibility Criteria

• Age: 1 Month - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Disease Status
• AML 1st complete remission (CR) with a matched family donor (excluding Downs Syndrome, acute promyelocytic leukaemia (APL), poor cytogenetics (12p, 5q, -7 and FMS-like tyrosine kinase 3 (FLT3) mutations or duplication t(9;11) and others)) and patients consented to and registered on an upfront AML COG study with a matched family donor)
• AML 1st CR (excluding Downs Syndrome, APL, and chromosome translocation (8;21) or inversion (16) or poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication t(9;11) and others)) with unrelated donor
• AML 2nd CR
• Myelodysplastic Syndrome (MDS) and ≤ 5% bone marrow myeloblasts at diagnosis (de novo patients only)
• Juvenile Myelomonocytic Leukemia (JMML) and ≤ 5% bone marrow myeloblasts at diagnosis
• In regards to disease immunophenotype, disease must express a minimum of ≥10% Cell Differential 33 (CD33) positivity for patients with AML
• Organ Function:
• Patients must have adequate organ function as defined below:
• Adequate renal function defined as:
• Serum creatinine \< 1.5 x normal, or
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) 40 ml/min/m2 or \> 60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
• Adequate liver function defined as total bilirubin 2.0 x upper limit of normal (ULN), or serum glutamic-oxaloacetic transaminase (SGOT)(aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT)(alanine aminotransferase (ALT)) \< 5.0 x ULN
• Adequate cardiac function defined as:
• Shortening fraction of ≥ 25% by echocardiogram, or

You may not qualify if:

• Patients with active central nervous system (CNS) AML/JMML disease at time of preparative regimen
• Secondary MDS
• Poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication)
• Female patients who are pregnant (positive human chorionic gonadotropin(hCG))
• Karnofsky \<70% or Lansky \<50% if 10 years or less
• Age \>30 years
• Seropositive for Human Immunodeficiency Virus (HIV)
• Patients consented to and registered on an upfront Children's Oncology Group (COG) AML study with a matched family donor

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Juvenile

Interventions

fludarabine; fludarabine phosphate; Busulfan; Gemtuzumab; Antilymphocyte Serum; thymoglobulin; Isotretinoin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Sera; Biological Products; Complex Mixtures; Retinoids; Carotenoids; Polyenes; Alkenes; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Monica Bhatia, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics, Section Head of Pediatric Stem Cell Transplant at Columbia University

Study Record Dates

• First Submitted: November 23, 2009
• First Posted: November 25, 2009
• Study Start: September 11, 2002
• Primary Completion: July 20, 2011
• Study Completion: December 1, 2020
• Last Updated: August 6, 2021

Record last verified: 2021-08

Locations

US (1)